Synthesis and antimicrobial testing of 2-substituted styryl-6-nitro-4-quinazolones.

Condensation of 2-methyl-6-nitro-4-quinazolone with different aldehydes was achieved by fusing the reactants in the presence of zinc chloride, affording 2-substituted styryl-6-nitro-4-quinazolones. 2-(3-substituted aminomethyl)-4-hydroxystyryl-6-nitro-4-quinazolones were also prepared through the Mannich reaction. The antimicrobial testing of five of the compounds prepared showed that some of them produce promising effects.     

Synthesis of thiadiazol derivatives of 4(3H)-quinazolinone as potential antimicrobial agents

Three series of quinazolinone derivatives were synthesised namely: 3-[4-(2-substituted amino-1,3,4-thiadiazol-5-yl)phenyl]-2-methyl-4-(3H)- quinazolinones; 3-[4-(2-substituted amino-1,3,4-thiadiazol-5-yl)anilino]-2-methyl-4-(3H)- quinazolinones and 3-[(2-substituted amino-1,3,4-thiadiazol-5-yl)methyl]-2-methyl-4(3H)-quinazolinones. The antimicrobial activity of representative compounds of these series as well as of the starting quinazolinone acids was studied.     

Synthesis and Antimicrobial Activities of Some New Azetidin-2-ones and Thiazolidin-4-ones

Various (4-substituted) phenyl-3-β-[(N-benzenesulphonyl/tosyl)-4-(un)substituted anilino]propionylamido-1,3-thiazolidine-4-ones (3a-x) and 1-β-[(N-benzenesulphonyl/tosyl)-4-(un)substituted anilino]-propionylamido-3-chloro-4-(4-substituted)phenyl-azetidin-2-ones (4a-x) have been synthesised by the cyclocondensation of Schiff bases (2a-x) with thioglycolic acid and chloroacetyl chloride, respectively. The structures of the newly synthesised compounds have been established on the basis of their spectral data and elemental analysis. All compounds were evaluated for antimicrobial activities against Escherichia coli, Bacillus cirroflagellosus, Aspergillus niger and Colletotrichum capsici. Most compounds investigated exhibited significant antifungal activity against Colletotrichum capsici, comparable to that of fluconazole, the standard used.     

Microwave induced diastereoselective synthesis of spiro[indole-oxiranes] and their conversion to spiro[indole-pyrazoles

The microwave induced diastereoselective synthesis of spiro[3H-indole-3,2'-oxiranes]-3'-benzoyl-2 (1H)-one is reported. Epoxidation of 3-aroylmethylene indole-2-one 1 with alkaline H2O2 under microwave irradiation in an open vessel under controlled conditions yields a diastereomeric pair of spiro[3H-indole-3,2'-oxiranes]-3'-benzoyl-2 (1H) ones 2 and 3 in 65-85% yield. The stereoselectivity depends upon the reaction time and power output. The spiro[indole-pyrazoles] 4 have been synthesised by the reaction of 2 with hydrazine hydrate. Under the same condition 3 gave the mixture of products. All synthesised compounds have been screened in vitro for their antifungal activity against Rhizoctonia solani, Fusarium oxysporum and Collectotrichum capsici and antitubercular activity against Mycobacterium tuberculosis.     

Synthesis of some new hydrazone derivatives as biologically active agents

A series of [4-(6H/bromo-4-oxo-2-phenyl-3(4H)-quinazolinyl)phenoxy]acetic acid (1,2-dihydro-1-H/methyl-2-oxo-3H-indol-3-ylidene)hydrazides (VII1-16) were synthesised by condensing 1-H/methyl-5-substituted indoline-2,3-diones with [4-(6H/bromo-4-oxo-2-phenyl-3(4H)-quinazolinyl) phenoxy]acetic acid hydrazides (IV1-2) which in turn were obtained by reacting ethyl [4-(6H/bromo-4-oxo-2-phenyl-3(4H)-quinazolinyl)phenoxy]acetates (III1-2) with hydrazine hydrate. All the synthesised compounds (VIII1-16) were screened for their antibacterial, acetylcholinesterase enzyme inhibitory and antiviral activities.     

Fluorinated quinazolones III: synthesis and CNS depressant activity of fluorinated quinazolone derivatives.

The synthesis of 2-allylthio-3-(4'-fluorophenyl)-5,6,7,8-tetrafluoro-4-quinazolone, 2-n-propylthio-3-(4'-fluorophenyl)-5,6,7,8-tetrafluoro-4-quinazolone, 3-(4'-bromophenyl)-5,6,7,8-tetrafluoro-2,4-quinazolinedithione, and seven fluorinated 2-alkyl/phenyl-3-aryl-4(3H)-quinazolones is described. The synthesized compounds were screened for CNS depressant activity using pentobarbital sleeping time, pentylenetetrazol convulsions, and condition avoidance test as the parameters. Most of the screened compounds exhibited significant depressant activity.     

Synthesis and in vitro antimycobacterial activity of 3-substituted 5-hydroxy-5-trifluoro[chloro]methyl-4,5-dihydro-1H-1-(isonicotinoyl) pyrazoles

A series of 3-substituted 5-hydroxy-5-trifluoro[chloro]methyl-1H-1-isonicotinoyl-4,5-dihydropyrazoles (2a-i) were synthesised by the cyclocondensation reaction of 4-methoxy-1,1,1-trifluoro[chloro]-4-(substituted)-alk-3-en-2-ones (1a-i) and isoniazid (INH). Their in vitro antimicrobial activity was tested against INH-susceptible Mycobacterium tuberculosis H37Rv, INH-resistant clinical M. tuberculosis isolates and non-tuberculous mycobacteria. Amongst the synthesised compounds, 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-(isonicotinoyl)-pyrazole (2a) and 5-hydroxy-3-(4-methylphenyl)-5-trifluoromethyl-4,5-dihydro-1H-1-(isonicotinoyl) pyrazole (2d) were found to be the two most active agents against susceptible M. tuberculosis and several INH-resistant strains. The compound 3-(2-furyl)-5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-(isonicotinoyl)pyrazole (2f) was active against all the INH-resistant strains regardless of the genetic background at concentrations two- to four-fold its minimum inhibitory concentration against M. tuberculosis H37Rv. These compounds were inhibitors of mycolic acid biosynthesis, in agreement with the utilisation of the INH scaffold for their design. Interestingly, the most active compound against M. tuberculosis, 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-(isonicotinoyl)-pyrazole (2a), was even more potent than INH against non-tuberculous mycobacteria.     

Synthesis and antimicrobial activity of some 1-(2,4-dinitrophenyl)-3-(3-nitrophenyl)-5-(4-substituted phenyl)-4-bromo-2-pyrazolines and 1-(2,4-dinitrophenyl)-3-(3-nitrophenyl)-5-(4-substituted phenyl)-2-pyrazolin-4-ones

A series of 1-(2,4-dinitrophenyl)-3-(3-nitrophenyl)-5-(4-substituted phenyl)-2-pyrazolin-4-ones (4a-e) have been synthesized by the oxidation of 1-(2,4-dinitrophenyl)-3-(3-nitrophenyl)-5-(4-substituted phenyl)-4-bromo-2-pyrazolines (3a-e) with dimethylsulfoxide. The structure has been established on the basis of spectral data (IR,1H NMR). The synthesized compounds have been screened in vitro for their possible antimicrobial activity.     

Synthesis and In Vitro Antioxidant Activity of New 3-Substituted-2-Oxindole Derivatives

A series of new 1,3-dihydro-3-hydroxy-3-(2-phenyl-2-oxoethyl)-2H-indol-2-ones (1a-g) and 1,3-dihydro-3-(2-phenyl-2-oxoethylidene)-2H-indol-2-ones (2a-g) were synthesised by Knoevenagel condensation of substituted indole-2,3-diones (isatins) with various acetophenones. The synthesised compounds were characterised by their physical data, elemental, IR, ¹H NMR, ¹³C NMR and mass spectral analyses and their in vitro antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay. These compounds showed moderate to good antioxidant activities as compared with the standard, ascorbic acid. The antioxidant potential of 3-hydroxy-3-substituted oxindoles (1a-g) increased in a concentration-dependent manner from 10 to 500 μg/ml with 5-fluoro and 5-methyl analogues showing maximum activity. Of 3-aroyl methylene indol-2-ones (2a-g), majority of compounds with halogen substitution at position 5 of isatin ring exhibited good antioxidant activity within a concentration range of 5-100 μg/ml and the maximum activity was observed at 20 and 25 μg/ml concentrations. Thus, our study provides evidence that some newly synthesised isatin derivatives exhibit substantial antioxidant activity at low concentrations.     

Quinazolyl benzophenothiazines as potential antiviral agents

The reaction of anthranilic acid with excess of benzoylchloride in the presence of pyridine yielded 2-phenyl(3H) 4-oxo-3,1-benzoxazine(I). Interaction of (I) with 2-aminoethanol afforded 2-phenyl-3-hydroxy-ethyl(3H) 4-oxo-quinazoline (II). The condensation of (II) with beta-naphthol in the presence of conc. H2SO4 gave 1-(2'-phenyl-3'-ethyl-4'-oxo-quinazolyl) beta-naphthol (III). The reaction of (III) with primary aromatic amines in the presence of anhydrous zinc-chloride afforded 1-(2'-phenyl-3'-ethyl-4'-oxo-quinazolyl)-beta-naphthyl phenyl amine (IV). When (IV) was heated with sulphur and iodine, 1-(2'-phenyl 3'-ethyl -4'-oxo-quinazolyl)-benzophenothiazine (V) was obtained. All the five synthesised benzophenothiazines were screened for their antiviral activity and two compounds exhibited significant inhibition of virus multiplications.     

4-difluoro-substituted phenl-5-oxohexahydroquinoline derivatives and their effects on calcium channels

Twenty new methyl(ethyl) 2,6,6- or 2,7,7-trimethyl-5-oxo-4-(disubstituted phenyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxylates and ten new N,N-diethyl-2,6,6- or 2,7,7-trimethyl-5-oxo-4-(disubstituted phenyl)-1,4,5,6,7,8-hexahydroquinoline-3-carboxamide derivatives have been synthesised and screened for their calcium channel antagonistic activity. The compounds were synthesised by the Hantzsch reaction. Calcium antagonistic activities of the compounds were determined by the tests performed on isolated rat ileum and rat thoracic artery.     

Synthesis, stereochemistry and anticonvulsant action of 4-phenyltetrahydroisoquinolines

The racemic and optically active 4'- and 8-substituted tetrahydroisoquinolines 2-5 have been synthesized and their effect on the water-immersion stress ulcer in rats has been studied. All compounds prevent the formation of stress ulcer, the strongest effect being exhibited by compound 4 and its dextrarotatory isomer (R1 = Cl, R2 = NHCOOC2H5). The antiulcer activity of 4 is 30 to 50 times higher than that of the H2 receptor antagonists Cimetidin and Ranitidin used for comparison. The absolute configuration of the optically active compounds 2, 3 and 4 has been determined by means of chemical correlation. The antiulcer activity of 4 is characterized by enantioselectivity, S-(+)-4 is three times as active than R-(-)-4.     

6-(4′-取代酰胺基苯基)-4,5-二氢-3(2H)-哒嗪酮类化合物的合成及其抑制血小板聚集作用

目的：6-(4′-取代苯基)-4,5-二氢-3(2H)-哒嗪酮类化合物的合成及抗血小板聚集活性的研究。方法：通过付-克反应、碳链延长、水解和环合反应得到两个关键中间体,然后通过酰化反应制得各种酰胺化合物;参考Born比浊法测定目标化合物的抗血小板聚集活性。结果：设计合成了24个6-(4′-取代酰胺基苯基)-4,5-二氢-3(2H)-哒嗪酮类化合物,22个为首次报道;所有化合物在体外对ADP诱导的兔血小板聚集均有不同程度的抑制作用,第II类化合物的抑制作用强于第I类化合物,其中I₁,I₃,II₁,II₃,II₄,II₆和II₉的抑制作用均强于对照药CI-930,其中II₁和II₃的抑制作用最强,其IC₅₀约为CI-930的1/10。结论：其中一些化合物显示较强的抗血小板聚集活性,值得进一步研究。     

Synthesis, antibacterial, antifungal and anti-HIV evaluation of Schiff and Mannich bases of isatin and its derivatives with triazole

Isatin (indole 2,3-dione) and its 5-chloro and 5-bromo derivatives have been reacted with 3-(4'-pyridyl)-4-amino-5-mercapto-4-(H)-1,2,4-triazole to form Schiff bases and the N-Mannich bases of these compounds were synthesised by reacting them with formaldehyde and several secondary amines. Their chemical structures have been confirmed by means of their IR, 1H-NMR data and by elemental analysis. Investigation of antimicrobial activity of compounds was done by agar dilution method against 27 pathogenic bacteria, 8 pathogenic fungi and anti-HIV activity against replication of HIV-1 (III B) in MT-4 cells. Among the compounds tested 1-(piperidinomethyl) 5-bromo 3-[3'-(4"-pyridyl)-5'-mercapto-4'-(H)-1',2',4'-triazol 4'-yl]imino isatin showed the most favourable antimicrobial activity.     

Synthesis and antihistaminic activity of some thiazolidin-4-ones.

A new series of 2-(4- and 3-substituted phenyl)-3-[3-(N,N-dimethylamino) propyl]-1,3-thiazolidin-4-ones were synthesized, characterized, and evaluated for their ability to inhibit the contractions induced by histamine on guinea pig ileum. The measurement of pA2 values suggested that the reported compounds showed H1-antagonism. The more active compounds 5, 9, and 13 exhibited activity close to that of mepyramine.     

Synthesis and antimicrobial activity of some new 3–[5-(4-substituted) phenyl-1,3,4-oxadiazole-2yl]-2- styrylquinazoline-4(3H)-ones

Several 3-[5-(4-substituted)phenyl-1,3,4-oxadiazole-2-yl]-2-styryl quinazoline-4(3H)-one were synthesized and screened for antibacterial activity against Staphylococcus aureus , Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli and antifungal activity against Aspergillus niger and Fusariumoxysporum by the serial dilution technique. Compounds were prepared by reacting corresponding 2-methtyl quinazolinone and 4-subustituted benzaldehydes in glacial acetic acid. Physicochemical and spectral data were consistent with newly synthesized compounds. The prepared compounds were compared with previously synthesized 2-methyl-3-[5-(4-substituted)phenyl-1,3,4-oxadiazole-2-yl]-quinazoline-4(3H)-ones for antimicrobial activity. The present study revealed that styryl moiety at the second position of 4(3H) quinazolinone marginally increased the biological activity and exhibited better antibacterial than antifungal activities.     

Synthesis and antihyperlipidemic activity of some novel condensed 2-chloroalkyl-4-chloro/hydroxy-5,6-disubstituted pyrimidines

Synthesis and antihyperlipidemic activity of a series of novel condensed 2-chloroalkyl-4-chloro/hydroxy-5,6-di-substituted pyrimidines are described. The design of these compounds is based on the earlier QSAR study on the antihyperlipidemic 2-substituted methylthienopyrimidin-4-ones. The newly synthesized condensed 4-chloro-2-chloroalkylpyrimidines (IIIa-n) have exhibited much superior antihyperlipidemic activity, compared to their earlier reported 4-hydroxy analogs. Notably, in this series, five compounds, IIIa, IIIb, IIIc, IIIi and IIIm showed good ability to reduce total cholesterol and two compounds, IIIa and IIIk exhibited better reduction in serum triglycerides. All the newly synthesized compounds have been evaluated by the Triton WR 1339 induced hyperlipidemia in albino Wistar rats model for antihyperlipidemic activity, and their activity is superior to that exhibited by the standard gemfibrozil used in the study. A 3D QSAR study has also been performed to delineate the effect of the substituents at 5 and 6 positions on the antihyperlipidemic activity of 2-chloromethyl-5,6-substituted thieno(2,3-d) pyrimidin-4(3H)-ones (IIa-e).     

Ether derivatives of 3-amino-1,2-propanediols, V. Syntheses and pharmacological activities of 5-(cycloalkoxymethyl)oxazolidines and N-substituted derivatives

The 5-(cycloalkoxymethyl)oxazolidines 5a, b and their N-substituted derivatives 3a–j were synthesized by reaction of the aminopropanols 4a, b and 2a–j with formaldehyde. Some of the compounds were found to have moderate β-blocking activity and 3b and 3h were found to have considerable antiarrhythmic activity.     

Synthesis of novel 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole derivatives as antiproliferative agents: A structure–activity relationship study

A series of novel 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole derivatives 5(a–m) were synthesized with different substituted aromatic/heterocyclic acid chlorides (R-CO-Cl) and characterized by ¹H NMR, LC/MS, FTIR and elemental analyses. All the compounds synthesised were evaluated for their antiproliferative activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The antiproliferative effects of the synthesised compounds were tested against viable human skin fibroblast cells and carcinoma cells namely HeLa cells, HT-29 cells, MCF-7 cells, HepG-2 cells by adopting positive and negative control. The importance of the aromatic and heterocyclic moiety was confirmed. From the SAR studies, it reveals that, the substitution at N-terminal of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole by the heterocyclic ring plays a dominant role and was responsible for the antiproliferative activity. Among the synthesized compounds 5a, 5d and 5k have showed potent antiproliferative activity on all the carcinoma cells tested.     

Antiparkinsonian activity and behavioural effects of newer quinazolinones

Sixteen new compounds 2-methylamino substituted phenyl-3-substituted anilino 4 (3H) quinazolinones (3-18) were prepared. All the compounds were evaluated for their antiparkinsonian activity and compared with bromocriptine. Compounds 10,15 and 18 showed better activity. These compounds also bind with the dopamine receptors in striatal membrane preparations of rat brain.